WHEN Dr. Morando Soffritti, a cancer researcher in Bologna, Italy,
saw the results of his team's seven-year study on aspartame,
he knew he was about to be injected into a bitter controversy
over this sweetener, one of the most contentiously debated substances
ever added to foods and beverages.

Pigi Cipelli for The New York Times
Dr. Morando Soffritti, who led tests of aspartame on 1,900 rats,
calls it a possible carcinogen. [ photo ]

Pigi Cipelli for The New York Times
A study conducted at an Italian cancer research center, above,
has rekindled the debate on aspartame. [ photo ]

Aspartame is sold under the brand names Nutra-Sweet and Equal
and is found in such popular products as Diet Coke, Diet Pepsi,
Diet Snapple and Sugar Free Kool-Aid.
Hundreds of millions of people consume it worldwide.
And Dr. Soffritti's study concluded that aspartame may cause
the dreaded "c" word: cancer.

The research found that the sweetener was associated
with unusually high rates of lymphomas, leukemias and other cancers
in rats that had been given doses of it starting at what would be
equivalent to four to five 20-ounce bottles of diet soda a day
for a 150-pound person.

The study, which involved 1,900 laboratory rats and cost $1 million,
was conducted at the European Ramazzini Foundation
of Oncology and Environmental Sciences, a nonprofit organization
that studies cancer-causing substances;
Dr. Soffritti is its scientific director.

The findings, first released last July, prompted a flurry of criticism
from the Calorie Control Council, a trade group for makers
of artificial sweeteners that has spent the last 25 years
trying to quell fears about aspartame.

It said Dr. Soffritti's study flew in the face of four earlier cancer
studies that aspartame's creator, G. D. Searle & Company,
had underwritten and used to persuade
the Food and Drug Administration to approve it for human consumption.

"Aspartame has been safely consumed for more than a quarter of a
century and is one of the most thoroughly studied food additives,"
read one news release from the council.

At the same time, Dr. Soffritti's findings have energized a vociferous
group of researchers, health advocates and others who say they are
convinced that aspartame is a toxin associated with a variety of
health troubles, including headaches, dizziness, blindness and seizures.

DR. SOFFRITTI, who oversees 180 scientists and researchers
in 30 countries who collaborate on toxin research,
says that since last July, he has been contacted by some of these critics,
including a member of Parliament in Britain and a number of
conspiracy theorists, some of whom say they have suffered from
"aspartame poisoning" and filled Web pages with cloak-and-dagger
speculation about why the F.D.A. approved aspartame for sale
a quarter-century ago.

No regulatory agency has yet acted on Dr. Soffritti's findings,
although Roger Williams, a member of Parliament,
called for a ban on aspartame in Britain last December.

Last month, the European Food Safety Authority,
an advisory body for the European Commission,
began to review 900 pages of data from Dr. Soffritti;
the goal is to finish by May.
A commission spokesman, Philip Tod, said it was too early
to know what the next steps would be if the scientists
reviewing the data concurred with Dr. Soffritti's findings.

In the United States, the Food and Drug Administration
says it has also taken note of the study, which is available online (
http://ehp.niehs.nih.gov/docs/2005/8711/abstract.html )
and is scheduled to be published next month in a medical journal
financed by the National Institutes of Health.

F.D.A. officials say that they, too, intend to conduct a thorough review.
But both the F.D.A. and the European Commission have cautioned
that there is no need for people to avoid aspartame.
"We don't see any concerns at this stage," said George H. Pauli,
associate director for science policy in the F.D.A.'s
Office of Food Additive Safety. "We've gone through a humongous
amount of data on aspartame over the years."

Putting restrictions on aspartame would come at a significant cost.
Food companies and consumers around the world bought
about $570 million worth of it last year.
New regulatory action on aspartame would also jeopardize
the billions of dollars worth of products sold with it.
Already, in the United States, many companies are opting to
use sucralose, or Splenda, in their new low-calorie products,
in part because it is less controversial.

[ Dr. Soffritti's journal article on his findings is at
nytimes.com/business ]

Lance Collins, chief executive of Fuze Beverage in Englewood Cliffs,
N.J., said that safety concerns about aspartame were a
"major contributing factor" in his decision to use sucralose
in his tea and juice drinks.

Sucralose, however, is made by under a patent by just one company,
Tate & Lyle of London, and is in desperately short supply.

Dr. Soffritti, who has spent 28 years doing research on potential
carcinogens, said he was trying to steer clear of the growing political
maelstrom. But he added that he was concerned about the large
numbers of people who use aspartame,
particularly children and pregnant women.
"If something is a carcinogen in animals," he said, "then it should not
be added to food, especially if there are so many people
that are going to be consuming it."

Lyn Nabors, executive vice president of the Calorie Control Council,
said Dr. Soffritti's study was not valid because the rats used
in it had been allowed to live longer than the two-year standard
established by the United States government's
National Toxicology Program. "It's difficult to determine if the cancers
you find are due to something else," Ms. Nabors said.
"Just as in humans, the rat's body slows down later in life,
and the aging process causes all kinds of things."

But John R. Bucher, deputy director of environmental toxicology
at the National Toxicology Program, the government's agency
for research on toxic chemicals, called the design of the Ramazzini
study "impressive" and "thorough," and said that he did not think
the fact that rats were allowed to live until their natural deaths
had skewed the results.

Dr. Jose Russo, director of the breast cancer and environmental
research center at the Fox Chase Cancer Center in Philadelphia,
says that lifetime studies are "ideal" but that they are not done often,
partly because they are more expensive than limited-time tests.
Dr. Russo, however, criticized the Ramazzini study for not allowing
outside pathologists to analyze all of the tissue samples where
cancerous tumors were found. "People need to see every tumor,"
he said.

Dr. Bucher of the National Toxicology Program said pathologists
at the program, with which Ramazzini collaborates, looked at 70
tumor slides.
But with the study producing over 9,000 tumor-containing slides,
James Swenberg, professor of environmental science
at the University of North Carolina at Chapel Hill,
says that this falls short of standard practice.

While Dr. Soffritti's methods have drawn some criticism,
the Ramazzini cancer lab, which is financed
by private bank foundations, governments and 17,000
individual members, has earned considerable credibility
since it was founded in 1971 for its pioneering research
on chemicals.

It was the first research body to do studies showing that
vinyl chloride and the gasoline additive methyl tertiary-butyl ether,
or M.T.B.E., are carcinogenic, research that eventually
encouraged the United States to strictly regulate vinyl chloride
and that led 21 states to ban M.T.B.E.

Dr. Soffritti said he was inspired to look at aspartame
because of what he calls "inadequacies" in the cancer studies done
by Searle in the 1970's. He said that those studies did not
involve large-enough numbers of rats and did not allow them
to live long enough to develop cancer.

The Ramazzini study was conducted with 1,900 rats,
as opposed to the 280 to 688 rodents used in Searle's studies,
and the rats lived for up to three years instead of being sacrificed
after two, which is the human equivalent of age 53.
"Cancer is a disease of the third part of life," Dr. Soffritti said.
"You have 75 percent of cancer diagnoses for people
who are 55 years old or older. So if you truncate the experiments
at 110 weeks and the rats are supposed to survive
until 150 to 160 weeks, it means you avoid the development
of cancer at the time when cancer would be starting to arise."

Others have also challenged Searle's studies.
Documents from the F.D.A. and records from the Federal Register
indicate that, in the years before the F.D.A. approved aspartame,
the agency had serious concerns about the accuracy and credibility
of Searle's aspartame studies. From 1977 to 1985 - during much
of the approval process - Searle was headed by
Donald H. Rumsfeld, who is now the secretary of defense;
Searle was acquired by Monsanto in 1985.

Monsanto later spun Searle's assets out into two companies:
Merisant, which owns the brands Equal and Canderel, and NutraSweet,
which is owned by J. W. Childs Equity Partners,
an investment firm in Boston.

A 1976 report from an F.D.A. task force, for example,
found that Searle's studies on aspartame and several of the company's
pharmaceutical drugs were "poorly conceived, carelessly executed, or
inaccurately analyzed or reported." It cited what it called a lack of
training by the scientists analyzing tissue samples, a "substantial"
loss of information because of tissue decomposition
and inadequate monitoring of feeding doses.

In response to the report, the F.D.A. asked the Justice Department
to open a grand jury investigation into whether two of Searle's
aspartame studies had been falsified or were incomplete.

In a 33-page letter in 1977, Richard A. Merrill, the F.D.A.'s
chief counsel at the time, recommended to Samuel K. Skinner,
then the United States attorney for the Northern District of Illinois,
that a grand jury investigate the company,
which was based in the Chicago suburb of Skokie,
for "concealing material facts and making false statements
in reports of animal studies conducted to establish the safety
of the drug Aldactone and the food additive aspartame."

A grand jury was never convened, however.
Shortly after the letter was sent, Mr. Skinner left the
Justice Department to join Sidley & Austin,
a law firm that represented Searle.

After 12 years at that firm, now Sidley, Austin, Brown & Wood,
Mr. Skinner was appointed to be President George H. W. Bush's
transportation secretary; later he became his chief of staff.

In 1978, a year and half after Mr. Skinner left the United States
attorney's office in Chicago, his deputy, William F. Conlon,
also left to work at Sidley & Austin.

Mr. Skinner, now a lawyer at Greenberg Traurig LLP,
said that as soon as he began looking for a new job
and interviewing with Sidley & Austin,
he recused himself from the Searle investigation.
Mr. Conlon, who is still at Sidley & Austin, did not return phone calls.

Over the next few years, Searle's petition for aspartame approval
led to much disagreement within the F.D.A.
The commissioner at the time, Alexander M. Schmidt,
convened a three-member public board of inquiry,
which concluded that one of Searle's studies on rats showed
an increase in brain tumors from aspartame.
The board members - all of them scientists at universities - voted
to withhold approval of aspartame until more studies were done.

But yet another F.D.A. review, this one of Searle's tumor tissue
slides - paid for by Searle and conducted by an academic group
that is now defunct - concluded that Searle's studies had
demonstrated that aspartame was safe.

In 1981, a new F.D.A. commissioner, Arthur Hull Hayes,
concurred with this assessment and granted approval to aspartame
shortly after President Ronald Reagan appointed him to run the agency.

And in a move that fueled the conspiracy theories,
Mr. Hayes left the F.D.A. a little more than a year after approving
aspartame and took a job as a consultant to Burson-Marsteller,
which at the time was Searle's public relations agency.
Mr. Hayes did not return calls seeking comment.

Ms. Nabors of the Calorie Control Council said that suggestions or
innuendoes that Searle was trying to influence government officials
with lucrative job offers were baseless. Artificial sweeteners are
unfairly targeted for suspicion, she said, citing the government's
decision to ban the sweetener cyclamate in 1969 after studies
showed that it caused cancer in animals. "Cyclamate was banned,
saccharin was required to have a warning label for a while,
and there's all these conspiracy theories on aspartame," she said.

She added that there were more than 100 published scientific studies
showing no adverse effects from aspartame, and said that in 2002,
the European Commission reviewed many of these studies and
reaffirmed the sweetener's safety. The bulk of the studies
investigated neurological effects; none were animal cancer studies,
which are lengthy and expensive.

In any case, critics say that most of these studies were financed either
directly or indirectly by manufacturers of aspartame, and that the results
of aspartame studies tend to depend on who paid for them.

In an analysis of 166 articles published in medical journals
from 1980 to 1985, Dr. Ralph G. Walton, a professor of psychiatry
at Northeastern Ohio Universities College of Medicine
found that all 74 studies that were financed by the industry
attested to sweetener's safety.

Of the 92 independently funded articles,
84 identified adverse health effects.
"Whenever you have studies that were not funded by the industry,
some sort of problem is identified," said Dr. Walton,
adding that he has not looked at studies performed since 1985.
"It's far too much for it to be a coincidence."

Dr. Walton, who, like some other psychiatrists, has studied aspartame
from a neurological perspective, said he had also seen problems from
the sweetener firsthand. At Safe Harbor Behavioral Health,
a mental health facility in Erie, Pa., where he is clinical director,
Dr. Walton said he had observed that for many people with mood
disorders, such as depression or bipolar disorder, aspartame
exacerbates the condition. "For people with panic disorders,
for instance, we've seen that when we eliminate aspartame,
it's much easier to control their illness," he said.
"The number of panic attacks goes down."

Dr. Walton and others say that this is probably attributable to
aspartame's phenyalanine component. (Aspartame is made up
of two amino acids, phenyalanine and aspartic acid.)
He said that an excess of phenyalanine could upset the body's
balance of neurotransmitters, causing a range of neurological symptoms.

Defenders of aspartame often point out that phenyalanine is naturally
present in many protein-intensive foods. But Dr. William M. Pardridge,
a professor of endocrinology at the David Geffen School of Medicine
at the University of California, Los Angeles, says that when it comes
from food, phenyalanine is absorbed into the brain more slowly.
"If your blood phenyalanine level was increased five times,
in my view there would be a safety concern," Dr. Pardridge said.
"The question is whether aspartame use could ever increase levels
that much, and the answer is yes. We've known that for 20 years."

Dr. Soffritti said he had not studied the effects of phenyalanine.
He theorized that the tumors in his study were related to the methanol,
or wood alcohol, that is produced as the body metabolizes aspartame.

When the body breaks down methanol, the result is formaldehyde,
a known carcinogen. "I know that when I treat animals with methanol,
you end up with lymphomas and leukemias," he said.

BUT Dr. Kenneth E. McMartin, a methanol expert and professor of
pharmacology, toxicology and neuroscience at the Louisiana State
University Medical Center, said he believed that it was unlikely
that someone could consume enough aspartame to let harmful levels
of formaldehyde build up in the body.

Dr. Soffritti said he thought that more research and open debate
were needed on whether aspartame was a carcinogen.
"It is very important to have scientists who are independent and
not funded by industry looking at this," he said.

Michael F. Jacobson, executive director of the
Center for Science in the Public Interest, a nutrition advocacy group,
said he did not think that Dr. Soffritti's study could be considered
definitive, but that it should prompt an "urgent re-examination.

"For a chemical that is used by hundreds of millions of people
around the world, it should be absolutely safe," Mr. Jacobson said.
"There shouldn't be a cloud of doubt."
************************************************** *****

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The manufacturer of Splenda, the brand name given to the chemical
sweetener sucralose, is releasing a version that can be used as a
replacement for brown sugar.
It will be called Splenda Brown Sugar Blend.

"People can use it for baking their favorite recipe or sprinkle it on top
of cereal the same way they would use brown sugar," said John Leahy,
marketing director for Splenda at McNeil Nutritionals,
the division of Johnson & Johnson that sells and markets the sweetener.

Made from a blend of regular brown sugar and sucralose that has been
colored brown, Splenda's brown sugar will give consumers a 50 percent
reduction in calories because a smaller amount will be needed for baking
and other purposes.

For instance, if a recipe calls for one cup of brown sugar, Mr. Leahy said, only a half-cup of Splenda brown sugar will be necessary.
Splenda brown sugar will come in one-pound and two-pound bags
when sales start in September.

The popularity of Splenda took its manufacturers by surprise last year.
In November, Tate & Lyle, the British ingredients company that makes
sucralose, told its customers that its supply of sweetener would have to
be rationed because of high demand. McNeil markets Splenda
in the United States under a contract with Tate & Lyle.

Over the last year and a half, nearly every major food company has
incorporated sucralose into one or more of its products. Both PepsiCo
and Coca-Cola have opted to use the sweetener for new colas.
This month, for example, Pepsi is introducing PepsiOne with Splenda
and Coke will make a new version of Diet Coke sweetened
with Splenda that will be in stores in several months.

Splenda brown sugar is likely to add to the legal debate brewing over
Splenda's marketing campaign. The Sugar Association, which represents
the sugar industry; Merisant, the maker of the aspartame-based
artificial sweetener NutraSweet; and a lawyer in San Diego
have filed lawsuits against McNeil contending that Splenda's
marketing misleads consumers.

"The average consumer assumes that Splenda is related to sugar,"
said Howard M. Rubinstein, the San Diego lawyer. "They're exploiting
the fear some people have around other artificial sweeteners
like NutraSweet and presenting this as a more natural alternative."

Mr. Leahy said that its marketing for the new brown sugar product
would "remain consistent with Splenda's existing brand communication."

Neither the Sugar Association, based in Washington, nor Merisant,
which is based in Chicago, would comment. If Splenda brown sugar
catches on with consumers, it is likely to accelerate the decline of
old-fashioned sugar.
Sales of both white and brown sugar in the United States have been
declining for years.
Sales have dropped 10 percent since 1999, Mintel International,
a research firm based in Chicago, has reported.
************************************************** *****

February 12, 2006

Any unsuspected source of methanol, which the body always quickly
and largely turns into formaldehyde and then formic acid, must be
monitored, especially for high responsibility occupations, often with
night shifts, such as pilots and nuclear reactor operators.

In particular, the next review gives many recent mainstream
peer-reviewed studies that show formaldehyde,
always inevitably derived in the body from any methanol source,
including aspartame, causes endothelial injury,
ie, diabetic neuropathy -- among the most serious and complex
complications of diabetes.

http://groups.yahoo.com/group/aspartameNM/message/1263
many studies on endothelial injury (diabetic neuropathy) by adducts of
formaldehyde derived from methylamine from many of the same sources
as also supply methanol (formaldehyde), including aspartame:
PH Yu et al: DJ Conklin et al: Murray 2005.12.04

http://groups.yahoo.com/group/aspartameNM/message/1237
ubiquitous potent uncontrolled co-factors in nutrition research are
formaldehyde from wood and tobacco smoke and many sources,
including from methanol in dark wines and liquors, in pectins
in fruits and vegetables, and in aspartame: Murray 2006.01.13

As a medical layman, I suggest that evidence mandates immediate
exploration of the role of these ubiquitious, potent formaldehyde
sources as co-factors in epidemiology, research, diagnosis,
and treatment in a wide variety of disorders.

Folic acid, from fruits and vegetables, plays a role by powerfully
protecting against methanol (formaldehyde) toxicity.

Many common drugs, such as aspirin, interfere with folic acid,
as do some mutations in relevant enzymes.

Aspartame is made of phenylalanine (50% by weight) and
aspartic acid (39%), both ordinary amino acids, bound
loosely together by methanol (wood alcohol, 11%).
The readily released methanol from aspartame is within hours
turned by the liver into formaldehyde and then formic acid,
both potent, cumulative toxins.
************************************************** *****

http://groups.yahoo.com/group/aspartameNM/message/1263
many studies on endothelial injury (diabetic neuropathy) by adducts of
formaldehyde derived from methylamine from many of the same sources
as also supply methanol (formaldehyde), including aspartame:
PH Yu et al: DJ Conklin et al: Murray 2005.12.04

"High or abuse concentrations of ASP hydrolysis products significantly
decreased the membrane enzyme activity,
which was completely or partially prevented by L-cysteine
or reduced GSH."

[ Definition of Erythrocyte
Erythrocyte:
A cell that contains hemoglobin and can carry oxygen to the body.
Also called a red blood cell (RBC).
The reddish color is due to the hemoglobin.
Erythrocytes are biconcave in shape,
which increases the cell's surface area
and facilitates the diffusion of oxygen and carbon dioxide.
This shape is maintained by a cytoskeleton
composed of several proteins.
Erythrocytes are very flexible
and change shape when flowing through capillaries.
Immature erythrocytes, called reticulocytes,
normally account for 1-2 percent of red cells in the blood. ]

Methods:
Erythrocyte [red blood cell] membranes
were obtained from 12 healthy individuals and
were incubated at 37 degrees C for 1 h
with the sum or each of the ASP metabolites separately,
which are commonly measured in blood after ASP ingestion.

Conclusions:
Low concentrations of ASP metabolites had no effect
on Na(+), K(+)-ATPase activity.

High or abuse concentrations of ASP hydrolysis products significantly
decreased the membrane enzyme activity,
which was completely or partially prevented by L-cysteine
or reduced GSH. [reduced glutathione]

However, a missed opportunity in both studies is that the inevitable,
extremely and cumulatively toxic products of methanol in the human
body, formaldehyde and formic acid, which are responsible for the
toxicity of methanol, were not independently tested.

" It is concluded that low concentrations of ASP metabolites had no
effect on the [human red blood cell] membrane enzyme activity,
whereas high or toxic concentrations partially or remarkably decreased
the [human red blood cell] membrane AChE activity, respectively.
Additionally, neurological symptoms, including learning and memory
processes, may be related to the high or toxic concentrations of the
sweetener metabolites. " ]

Studies have implicated aspartame (ASP) with neurological problems.
The aim of this study was to evaluate acetylcholinesterase (AChE)
activity in human erythrocyte [red blood cell] membranes
after incubation with the sum of ASP metabolites,
phenylalanine (Phe),
methanol (met) and
aspartic acid (aspt),
or with each one separately.

It is concluded that low concentrations of ASP metabolites had
no effect on the membrane enzyme activity,
whereas high or toxic concentrations partially or remarkably
decreased the membrane AChE activity, respectively.
Additionally, neurological symptoms, including learning and memory
processes, may be related to the high or toxic concentrations of the
sweetener metabolites. PMID: 16129618
************************************************** ****

Rich Murray: I have corrected typos and spelling, and added spacing
to improve readability. I found abstracts for 7 of the 9 references, and
added more abstracts that show a vigorous scientific advance, with
scores of scientists and studies. These studies may well be relevant
to very recent research that aspartame hurts memory in rats:

Recently, much controversy has surrounded a claim that aspartame
may produce an MS-like syndrome.
A current review of recent peer-reviewed scientific studies have
disclosed a pathophysiological mechanism to explain this connection.

As far back as 1996 it was shown that the lesions produced in the
myelin sheath of axons in cases of multiple sclerosis were related to
excitatory receptors on the primary cells involved, called
oligodendroglia.
Recent studies have now confirmed what was suspected back then.
The loss of myelin sheath on the nerve fibers characteristic of the
disease are due to the death of these oligodendroglial cells at the site
of the lesions (called plaques). Further, these studies have shown
that the death of these important cells is as a result of excessive
exposure to excitotoxins at the site of the lesions.

Normally, most of these excitotoxins are secreted from microglial
immune cells in the central nervous system.
This not only destroys these myelin-producing cells, it also breaks
down the blood-brain barrier (BBB), allowing excitotoxins in the
blood stream to enter the site of damage.

Aspartame contains the excitotoxin aspartate as 40% of its
molecular structure. Numerous studies have shown that consuming
aspartame can significantly elevate the excitotoxin level in the blood.

[ Rich Murray: A Searle Laboratories team in 1976 reported that
in 4 monkeys fed aspartame, by 12 hours: "...the major fraction
(70%) of the [aspartate] label appeared in the expired air (Fig.6)...
Urinary and fecal 14C [ aspartate derived ] amounted to 4--6%
of the administered [ aspartate ] label."
This gives a total of a maximum 76% excreted aspartate
from the aspartame, indicating that 24% of this excitotoxin
was retained in the body.
It is reasonable to conclude that daily use of aspartame must lead to
substantial accumulation of this excitotoxin, aspartate, in body tissues.

Their 1979 review said: "Aspartame... is hydrolyzed in the gut to yield
aspartic acid, phenylalanine, and methanol....
Aspartate may also be incorporated into body constitutents such as
other amino acids, proteins, pyrimidines, asparagine, and
N-acetylaspartic acid."

Aspartame (3-amino-N-(alpha-carboxyphenethyl) succinamic acid,
methyl ester; the methyl ester of aspartylphenylalanine, SC-18862)
is hydrolyzed in the gut to yield aspartic acid, phenylalanine,
and methanol.
This review of the literature describes the metabolic paths
followed by aspartate in its conversion to CO2
or its incorporation into body constituents.
About 70 percent of 14C from [asp-14C]-aspartame is
converted in the monkey to 14CO2.
Some of the aspartate is converted at the intestinal mucosal level to
alanine by decarboxylation.
This amino acid may be oxidized to CO2 by entering the
tricarboxylic acid cycle via pyruvate and acetyl CoA.
In addition, transamination of aspartate to oxaloacetate
permits this product also to enter the tricarboxylic acid cycle.
Aspartate may also be incorporated into body constitutents such as
other amino acids, proteins, pyrimidines, asparagine,
and N-acetylaspartic acid.
It is concluded that the aspartate moiety of aspartame
is metabolized in a manner similar to that of dietary aspartic acid.
Publication Types: Review PMID: 376770 ]

There is a common situation during which the excitotoxin
exposure is even greater.
When aspartate (as aspartame) is combined in the diet with
monosodium glutamate (MSG) blood levels are several fold higher
than normal.
With the BBB damaged, as in MS, these excitotoxins can freely enter
the site of injury, greatly magnifying the damage.
So, we see that dietary excitotoxins, such as aspartame and MSG,
can greatly magnify the damage produced in multiple sclerosis.
Likewise, excitotoxins have been shown to breakdown the BBB as well.

Of equal concern is observation that we know that about 10% of the
population (based on autopsy studies of elderly) have MS lesions without
ever developing the full blown disease,
a condition called benign MS.

A diet high in excitotoxins, such as aspartame, can convert this benign,
subclinical condition into full-blown clinical MS.
The amount of excitotoxins consumed in the average American diet is
considerable, as shown by several studies.

In addition, the toxin methanol is also in the aspartame molecule.
Methanol is an axon poison.
Combined toxicity of the aspartate and the methanol adds up to
considerable brain toxicity, and can convert benign, subclinical MS
into full-blown MS.
Once the MS becomes full-blown, further consumption of
excitotoxins magnifies the toxicity, increasing disability and death.

Recent studies have also shown that even single exposures to these
food-based excitotoxins can produce prolonged worsening of
neurological lesions.

In addition, it has been demonstrated that autoimmune reactions
(as occurs with MS) greatly magnifies the toxicity of aspartate
and glutamate (the excitotoxins).

We also know liquid forms of excitotoxins are significantly more
toxic because of rapid absorption and higher blood levels.

In the face of this connection between excitotoxicity and the
pathophysiology of MS, it would be ludicrous to allow further use
of this excitotoxin containing sweetener.

TREATMENT FOR MS:
It is now known the cause for the destruction of the myelin in the
lesions is overactivation of the microglia in the region of the myelin.
An enzyme that converts glutamine to glutamate, called glutaminase,
increases tremendously, thereby greatly increasing excitotoxicity.

Mercury also activates microglia, even in subtoxic doses.

Any dietary excitotoxin can activate the microglia, thereby greatly
aggravating the injury.
This includes the aspartate in aspartame.
The methanol adds to this toxicity as well.

Now, the secret to treatment appears to be shutting down, or at least
calming down, the microglia.
It has been found that the antibiotic minocycline powerfully shuts
down the microglia.
I tried this treatment on a friend of mine who just came down with
fulmanant MS.
He was confined to a wheelchair.
I had him placed on minocycline and now, just a few weeks later,
he is walking.

The good news is that other things also calm the microglia --
the most potent are: silymarin, curcumin and ibuprophen.
Phosphatidylcholine helps re-myelinate the nerve sheaths that are
damaged, as does B12, B6, B1, vitamin D, folate, vitamin C,
natural vitamin E (mixed tocopherols) and L-carnitine.

DHA plays a major role in repairing the myelin sheath.

Vitamin D may even prevent MS, but it acts as an immune modulator,
preventing further damage -- the dose is 2000 IU a day.

Magnesium, as magnesium malate, is needed
in a dose of 500 mg 2X a day.

They must avoid all excitotoxins, even natural ones in foods --
such as soy, red meats, nuts, mushrooms and tomatoes.

Avoid all fluoride and especially all vaccinations, since these
either inhibit antioxidant enzymes or trigger harmful immune reactions.

Dr. Blaylock is a recently retired board-certified neurosurgeon
with more than twenty six years experience. He is a recently retired
Clinical Assistant Professor of Neurosurgery at the Medical University
of Mississippi. Author of thirty scientific papers on various medical
subjects, chapters in three medical textbooks and a booklet on multiple
sclerosis, he recently completed a booklet on bioterrorism and is the
author of "Excitotoxins: The Taste That Kills",
"Health & Nutrition Secrets to Save Your Life", and
"Natural Strategies for Cancer Patients".
http://www.russellblaylockmd.com/
He serves on the editorial staff of The Journal of American Physicians
and Surgeons, the Journal of the American Nutraceutical Association,
and acts as a medical advisor to the American Nutraceutical Association.
His excellent newsletter can be gotten at
http://www.blaylockreport.com/
He lives in Ridgeland, Mississippi.

Recent studies indicate that oligodendrocytes are vulnerable to
excitotoxic insults mediated by glutamate receptors.
The present study was carried out to characterize the type of glutamate
receptors triggering cell death in optic nerve oligodendrocyte cultures.
Acute activation of either AMPA or kainate receptors was toxic to
oligodendrocytes, an effect that was prevented by CNQX.
However, exposure to agonists of the NMDA and metabotropic
glutamate receptors did not impair cell viability.
Dose-response curves showed that toxicity was mediated
by three distinct populations of receptors:
an AMPA-type receptor and high- and low-affinity kainate-type
receptors.
Expression and immunocytochemical studies suggested that the
glutamate receptor subunits give rise to the native receptors
in each population.
In all instances, Ca(2+) entry was a major determinant
of glutamate receptor excitotoxicity.
However, its influence varied for each receptor subtype.
These results indicate that aberrantly enhanced activation of
AMPA and/or kainate receptors may be involved
in demyelinating diseases.
Copyright 1999 Academic Press. PMID: 10600403

Oligodendrocytes are vulnerable to excitotoxic signals mediated
by AMPA receptors and by high- and low-affinity kainate receptors.
Here we investigated the nature of the cell death triggered by activation
of these receptors in primary cultures of oligodendrocytes
from the rat optic nerve.
Activation of AMPA receptors at both submaximal and maximal
concentrations of the agonist induced massive calcium entry,
mitochondrial depolarization, and a rise in the level of reactive oxygen
species that correlated with a decrease in the levels of reduced
glutathione.
In addition, excitotoxicity initiated by submaximal, but not maximal,
activation of AMPA receptors was prevented by caspase-3 blockade
and by the concomitant blockade of caspases 8 and 9.
In turn, maximal activation of high- or low-affinity kainate receptors
induced mitochondrial events and toxicity levels similar to those observed
with submaximal activation of AMPA receptors.
In contrast to AMPA receptor-mediated insults, calcineurin inhibition
or caspase-9 blockade was sufficient to prevent cell death triggered
by both types of kainate receptors.
Consistent with these results, prolonged glutamate receptor activation in
freshly isolated optic nerves caused selective activation of caspase-3
and chromatin condensation in oligodendrocytes.
Overall, the evidence presented here indicates that oligodendrocyte
death by excitotoxicity is mediated
by caspase-dependent and -independent mechanisms.
PMID: 14573531

A role for neuropeptide receptors in glial tumorigenesis has recently
been proposed.
Although angiotensin receptors are known to mediate proliferative
effects in many cell types, including brain astrocytes, the possible
participation of these receptors in glial tumorigenesis remains unknown.
In the present study, we have examined the expression of the molecularly
defined angiotensin receptor subtypes AT(1a), AT(1b), and AT(2) in
normal perinatal rat astrocytes
and in a panel of tumor adult astrocytoma cells,
using the reverse transcriptase-polymerase chain reaction (RT-PCR).
Subsequently, we compared the mitogenic effect of the angiotensins
A(1-8), A(2-8), A(3-8) and the heptapeptide "metabolite" A(1-7),
on both normal and tumor astrocytes,
measured in terms of the incorporation of tritiated thymidine.
Our results indicate that AT(1a), AT(1b), and AT(2) angiotensin
receptor mRNA is commonly expressed by many of these cells.
Of notable exception is the astrocytoma U373 which was not found
to express AT(1) or AT(2) mRNA.
Chronic (24-h) incubation of cells with A(1-8) and A(1-7) lead to the
induction of mitogenesis, even in the AT(1) and AT(2) mRNA negative
astrocytoma cell line U373.
Moreover, pharmacological analysis indicated that the observed
mitogenic effects are not mediated by the AT(1) or AT(2) type
receptors, but rather by a novel, specific A((1-7)) angiotensin
receptor, since mitogenesis was shown
to be partially blocked by the A(1-7) analogue D-Ala(7)A(1-7)
and by the protease inhibitor orthophenanthroline (100 microM).
Using Fura-2 spectrophotometry, we found that activation of this
receptor does not alter intracellular calcium levels;
however, preincubation with the protein kinase kinase inhibitor
U0126 (10 microM) was found to inhibit these mitogenic effects
partially.
Overall, these results which demonstrate that normal and tumor
astrocytes express a greater variety of angiotensin receptor subtypes
than previously thought,
support the idea that A(1-7) and its receptor signaling system may
play an important role in shaping the astrocyte population during
development.
Moreover, the untimely expression of this A((1-7)) receptor
may represent an important etiological component in the development
of brain astrocytomas.
Copyright 2002 Wiley-Liss, Inc. PMID: 12203396

Excitotoxicity results from prolonged activation of glutamate receptors
expressed by cells in the central nervous system (CNS).
This cell death mechanism was first discovered in retinal ganglion cells
and subsequently in brain neurons.
In addition, it has been recently observed that CNS glial cells can also
undergo excitotoxicity.
Among them, oligodendrocytes are highly vulnerable to glutamate signals
and alterations in glutamate homeostasis may contribute to demyelinating
disorders.
We review here the available information on excitotoxity in CNS glial
cells and its putative relevance to glio-pathologies. PMID: 12151015

Oligodendrocytes, the myelinating cells of CNS axons, are highly
vulnerable to excitotoxic signals mediated by glutamate receptors of the
AMPA and kainate classes.
Receptors in these cells are commonly activated by glutamate that is
released from axons and glial cells.
In addition, oligodendrocytes contribute to the control of extracellular
glutamate levels by means of their own transporters.
However, acute and chronic alterations in glutamate homeostasis
can result in overactivation of AMPA and kainate receptors
and subsequent excitotoxic oligodendroglial death.
Furthermore, demyelinating lesions caused by excitotoxins
can be similar to those observed in multiple sclerosis.
This, together with the effect of AMPA and kainate receptor
antagonists in ameliorating the neurological score of animals with
experimental autoimmune encephalomyelitis
(an animal model of multiple sclerosis), indicates that
oligodendrocyte excitotoxicity could be involved in the pathogenesis of
demyelinating disorders. Publication Types: Review Review Literature
PMID: 11250007

Glial cells communicate reciprocally with neurons in multiple ways,
both in synaptic and non-synaptic regions of the central nervous system.
In the latter, neuron to glial and glial to glial signals can be mediated by
neurotransmitters.
Here, we review the presence and some of the functional properties of
glutamate transporters and receptors in oligodendrocytes.
In addition, we present data illustrating that alterations in glutamate
homeostasis can be excitotoxic to oligodendroglia and that the tissue
lesions caused by overactivation of glutamate receptors resemble those
observed in demyelinating diseases such as multiple sclerosis.
Overall, this information indicates that aberrant glutamate signaling may
contribute to the development of some white matter pathologies.
Publication Types: Review Review, Tutorial PMID: 10635022

From the Departments of Pharmacology, § Neurology, ¶ Pediatrics,
Pathology and Laboratory Medicine, University of Pennsylvania School
of Medicine, Children's Seashore House,
Philadelphia, Pennsylvania 19104
DAVID E PLEASURE pleasure@email.chop.edu 215-590-2090

N-methyl-D-aspartate (NMDA) receptors can mediate cell death
in neurons and in non-neuronal cells that express recombinant NMDA
receptors.
In neurons, increases in intracellular calcium correlate with NMDA
receptor-mediated death, supporting a key role for loss of cellular
calcium homeostasis in excitotoxic cell death.
In the present study, free intracellular calcium concentrations were
examined in response to activation of recombinant NMDA receptors
expressed in human embryonic kidney 293 cells.
Intracellular calcium was measured in transfected cell populations by
cotransfection with the calcium-sensitive, bioluminescent protein aequorin
and by single cell imaging with the fluorescent calcium indicator fluo-3.
Agonist application to NR1/2A or NR1/2B-transfected cells elicited
robust rises in intracellular calcium.
NR1/2A responses were inhibited by the noncompetitive antagonists
MK-801 and dextromethorphan and were dependent on extracellular
calcium but not on intracellular calcium stores.
In contrast, no detectable intracellular calcium responses were observed
in NR1/2C-transfected cells.
These findings indicate that NMDA receptors in the absence of other
neuron-specific factors can mediate increases in intracellular calcium with
subunit specificity and extracellular calcium dependence.
PMID: 8995308

Since excitotoxicity has been implicated in a variety of neuropathological
conditions, understanding the pathways involved in this type of cell death
is of critical importance to the future clinical treatment of many diseases.
The N-methyl-D-aspartate (NMDA) receptor has become a primary
focus of excitotoxic research because early studies demonstrated that
antagonism of this receptor subtype was neuroprotective.
However, initial pharmacological agents were not clinically useful due to
the adverse effects of complete NMDA receptor blockade.
Understanding the biochemical properties of the multitude of NMDA
receptor subtypes offers the possibility of developing more effective and
clinically useful drugs. With the discovery of the basis of heterogeneity
of NMDA receptors through molecular biological approaches,
many new potential therapeutic targets have been uncovered,
and several model systems have been developed for the study of
NMDA receptor-mediated cell death.
This review discusses these models and the current understanding
of the relationship between NMDA receptor subtypes and excitotoxicity.

Myelination of axons is important for central nervous system function,
but oligodendrocytes, which constitute CNS myelin, are vulnerable
to excitotoxic injury and death.
Although mature oligodendrocytes express functional
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA)
and kainate-type glutamate receptors, the relative roles of these
subtypes in excitotoxicity are not well understood.
Using recently developed selective antagonists for subtypes of
ionotropic non-NMDA receptors, we addressed this issue.
By examining the pharmacological, biochemical, and morphologic
features of kainite-induced excitotoxic death, we also determined
whether it occurs by apoptosis, necrosis, or both.
We conclude that when mature oligodendrocytes die after exposure
to kainate:
(1) AMPA receptors are the most important mediators,
(2) kainate receptors play a smaller role, and
(3) death occurs predominantly by necrosis, not apoptosis.
PMID: 14678751

Glutamate excitotoxicity is implicated in the progressive loss of
oligodendrocytes in multiple sclerosis, but how glutamate metabolism
is dysregulated in the disease remains unclear.
Because there is microglia activation in all stages of multiple sclerosis,
we determined whether a microglia product, interleukin-1,
could provide the mechanism for glutamate excitotoxicity.
We found that whereas interleukin-1 did not kill oligodendrocytes
in pure culture, it produced apoptosis of oligodendrocytes in coculture
with astrocytes and microglia.
This requirement for a mixed glia environment suggests that interleukin-1
impairs the well-described glutamate-buffering capacity of astrocytes.
In support, antagonists at AMPA/kainate glutamate receptors,
NBQX and CNQX,
blocked the interleukin-1 toxicity to oligodendrocytes.
Another microglia/macrophage cytokine, tumor necrosis factor-,
also evoked apoptosis of oligodendrocytes in a mixed glia environment
in an NBQX-blockable manner.
These results provide a mechanistic link between the persistent and
insidious microglia activation that is evident in all stages of multiple
sclerosis, with the recent appreciation that glutamate excitotoxicity leads
to the destruction of oligodendrocytes in the disease.

BACKGROUND:
Excitotoxic damage is a common pathologic event in a number of
neurologic diseases occurring after accumulation of excess extracellular
glutamate in the CNS and subsequent overstimulation
of glutamate receptors.
In gray matter, astrocytes take up synaptically released glutamate
and are thus key cells in maintaining glutamate homeostasis.
In white matter, oligodendrocytes have been shown to express
glutamate transporters, but their role in extracellular glutamate
removal is unclear.
OBJECTIVE:
To investigate whether cultured human fetal oligodendrocytes
functionally express the main glutamate transporters
EAAT-1 and EAAT-2.
METHODS:
Cultures of fetal human oligodendrocytes were examined by
immunocytochemistry and [3H]glutamate uptake, and the findings were
correlated with glutamate transporter expression in normal and multiple
sclerosis (MS) CNS tissue.
RESULTS:
Both EAAT-1 and EAAT-2 were expressed
by human oligodendrocytes in vitro.
Incubation of oligodendrocytes with the proinflammatory cytokine
tumor necrosis factor-alpha (TNFalpha) reduced EAAT-1 expression
and inhibited glutamate uptake by &gt;75%.
Furthermore, in normal human white matter, oligodendrocytes
were found to be the predominant cells to express
EAAT-1 and EAAT-2, both at the mRNA and at the protein level.
A small number of astrocytes in white matter expressed these receptors,
more so EAAT-1 than EAAT-2.
In MS white matter, oligodendrocytes lost expression of
EAAT-1 and EAAT-2 receptors in the lesion vicinity.
CONCLUSIONS:
Oligodendrocytes appear to be predominant cells for glutamate
clearance in human white matter.
Glutamate receptor expression and glutamate removal were defective
in MS white matter, possibly mediated by TNFalpha, changes that
might underlie high extracellular glutamate and an increased risk for
glutamate excitotoxicity. PMID: 1458167

Excitotoxic oligodendroglial death is one of the mechanisms which
has been proposed to underlie demyelinating diseases of the CNS.
We describe here functional consequences of excitotoxic lesions to the
rabbit optic nerve by studying the visual evoked potentials (VEPs)
measured in the visual cortex.
Nerves were slowly infused with the excitotoxin kainate a
subcutaneously implanted osmotic pump which delivered the
toxin through a cannula onto the optic nerve.
Records of VEPs were obtained before pump implantation and at
1, 3 and 7 days post-implantation, and weekly evaluated thereafter
for up to 4 months.
We observed that the VEPs generated by light stimuli progressively
changed in both amplitude and profile after the lesion as well as in
comparison to those generated in control animals infused with vehicle.
Histological examination of the damage caused by the excitotoxic insult
showed that large areas of the optic nerve were demyelinated and their
axons distorted.
These observations were confirmed and extended by
immunohistochemical analyses using markers to neurofilaments,
myelin basic protein and the oligodendrocyte marker APC.
The results of the present paper indicate that the consequences of
excitotoxicity in the optic nerve share functional and morphological
alterations which are found in demyelinating disorders.
In addition, this experimental paradigm may be useful to evaluate the
functional recovery of demyelinated optic nerves following various
repair strategies. PMID: 14698751

Any unsuspected source of methanol, which the body always quickly
and largely turns into formaldehyde and then formic acid, must be
monitored, especially for high responsibility occupations, often with
night shifts, such as pilots and nuclear reactor operators.

In particular, the next review gives many recent mainstream
peer-reviewed studies that show formaldehyde,
always inevitably derived in the body from any methanol source,
including aspartame, causes endothelial injury,
ie, diabetic neuropathy -- among the most serious and complex
complications of diabetes.

http://groups.yahoo.com/group/aspartameNM/message/1263
many studies on endothelial injury (diabetic neuropathy) by adducts of
formaldehyde derived from methylamine from many of the same sources
as also supply methanol (formaldehyde), including aspartame:
PH Yu et al: DJ Conklin et al: Murray 2005.12.04

http://groups.yahoo.com/group/aspartameNM/message/1237
ubiquitous potent uncontrolled co-factors in nutrition research are
formaldehyde from wood and tobacco smoke and many sources,
including from methanol in dark wines and liquors, in pectins
in fruits and vegetables, and in aspartame: Murray 2006.01.13

As a medical layman, I suggest that evidence mandates immediate
exploration of the role of these ubiquitious, potent formaldehyde
sources as co-factors in epidemiology, research, diagnosis,
and treatment in a wide variety of disorders.

Folic acid, from fruits and vegetables, plays a role by powerfully
protecting against methanol (formaldehyde) toxicity.

Many common drugs, such as aspirin, interfere with folic acid,
as do some mutations in relevant enzymes.

Aspartame is made of phenylalanine (50% by weight) and
aspartic acid (39%), both ordinary amino acids, bound
loosely together by methanol (wood alcohol, 11%).
The readily released methanol from aspartame is within hours
turned by the liver into formaldehyde and then formic acid,
both potent, cumulative toxins.

http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame
(methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21
[ Any scientist can get access to this data for free by submitting a proper
research proposal.
No one has admitted mining the extensive data on diet soda use
and many symptoms for decades for about 100,000 nurses. ]

Thrasher (2001): "The major difference is that the Japanese
demonstrated the incorporation of FA and its metabolites into the
placenta and fetus.
The quantity of radioactivity remaining in maternal and fetal tissues
at 48 hours was 26.9% of the administered dose." [ Ref. 14-16 ]

http://groups.yahoo.com/group/aspartameNM/message/1237
ubiquitous potent uncontrolled co-factors in nutrition research are
formaldehyde from wood and tobacco smoke and many sources,
including from methanol in dark wines and liquors, in pectins
in fruits and vegetables, and in aspartame: Murray 2006.01.13

Since no adaquate data has ever been published on the exact
disposition of toxic metabolites in specific tissues in
humans of the 11% methanol component of aspartame, the many
studies on morning-after hangover from the methanol impurity
in alcohol drinks are the main available resource to date.